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vitamin B12





vitamin B12 molecular structure
Vitamin B12, also known as cyanocobalamin or cobalamin (because it contains the metal cobalt), is a constituent of the vitamin B complex. It plays an essential role in the activities of several enzymes. It is important in the functioning of the nervous system, the production of red blood cells and the genetic material of cells (DNA). It is also important in the utilization of folic acid (another member of the vitamin B complex) and carbohydrates in the diet.

Vitamin B12 is bound to the protein in food. Hydrochloric acid in the stomach releases vitamin B12 from proteins in foods during digestion. Once released, vitamin B12 combines with a substance called intrinsic factor (IF). This complex can then be absorbed by the intestinal tract.


Dietary sources of vitamin B12

Vitamin B12 is naturally found in foods that come from animals, including fish, meat, poultry, eggs, milk, and milk products. Fortified breakfast cereals are a particularly valuable source of vitamin B for vegetarians. Table 1 lists a variety of food sources of vitamin B12.





Table 1: Selected food sources of vitamin B12
Food Micrograms (g) per serving Percent (DV*)
Mollusks, clam, mixed species, cooked, 3 ounces 84.1 1400
Liver, beef, braised, 1 slice 47.9 780
Fortified breakfast cereals, (100%) fortified), ¾ cup 6.0 100
Trout, rainbow, wild, cooked, 3 ounces 5.4 90
Salmon, sockeye, cooked, 3 ounces 4.9 80
Trout, rainbow, farmed, cooked, 3 ounces 4.2 50
Beef, top sirloin, lean, choice, broiled, 3 ounces 2.4 40
Fast Food, Cheeseburger, regular, double patty & bun, 1 sandwich 1.9 30
Fast Food, Taco, 1 large 1.6 25
Fortified breakfast cereals (25% fortified), ¾ cup 1.5 25
Yogurt, plain, skim, with 13 grams protein per cup, 1 cup 1.4 25
Haddock, cooked, 3 ounces 1.2 20
Clams, breaded & fried, ¾ cup 1.1 20
Tuna, white, canned in water, drained solids, 3 ounces 1.0 15
Milk, 1 cup 0.9 15
Pork, cured, ham, lean only, canned, roasted, 3 ounces 0.6 10
Egg, whole, hard boiled, 1 0.6 10
American pasteurized cheese food, 1 ounces 0.3 6
Chicken, breast, meat only, roasted, ½ breast 0.3 6
*DV = Daily Value. DVs are reference numbers developed by the Food and Drug Administration (FDA) to help consumers determine if a food contains a lot or a little of a specific nutrient. The DV for vitamin B12 is 6.0 micrograms (g). Most food labels do not list a food's vitamin B12 content. The percent DV (%DV) listed on the table indicates the percentage of the DV provided in one serving. A food providing 5% of the DV or less is a low source while a food that provides 10% to 19% of the DV is a good source. A food that provides 20% or more of the DV is high in that nutrient. It is important to remember that foods that provide lower percentages of the DV also contribute to a healthful diet.


What is the recommended dietary intake for vitamin B12?

Recommendations for vitamin B12 are provided in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine of the National Academies. Dietary Reference Intakes is the general term for a set of reference values used for planning and assessing nutrient intake for healthy people. Three important types of reference values included in the DRIs are Recommended Dietary Allowances (RDA), Adequate Intakes (AI), and Tolerable Upper Intake Levels (UL). The RDA recommends the average daily intake that is sufficient to meet the nutrient requirements of nearly all (97% to 98%) healthy individuals in each age and gender group. An AI is set when there is insufficient scientific data available to establish an RDA. AIs meet or exceed the amount needed to maintain a nutritional state of adequacy (see nutrition) in nearly all members of a specific age and gender group. The UL, on the other hand, is the maximum daily intake unlikely to result in adverse health effects. Table 2 lists the RDAs for vitamin B12, in micrograms, for children and adults.


Table 2: Recommended Dietary Allowances (RDA) for vitamin B12 for children and adults
Age (years) Males and Females (g/day) Pregnancy (g/day) Lactation (g/day)
1-3 0.9 N/A N/A
4-8 1.2 N/A N/A
9-13 1.8 N/A N/A
14-18 2.4 2.6 2.8
19 and older 2.4 2.6 2.8


Information on vitamin B12 is insufficient to establish an RDA for infants. Therefore, an AI has been established that is based on the amount of vitamin B12 consumed by healthy infants who are fed breast milk. Table 3 lists the AIs for vitamin B12, in micrograms, for infants.


Table 3: Adequate Intake (AI) for vitamin B12 for infants
Age(months) Males and Females g/day)
0-6 months 0.4
7-12 months 0.5


When is a deficiency of vitamin B12 likely to occur?

Results of two national surveys in the United States, the National Health and Nutrition Examination Survey (NHANES III-1988-94) and the Continuing Survey of Food Intakes by Individuals (CSFII 1994-96) found that most children and adults in the US consume recommended amounts of vitamin B12. A deficiency may still occur as a result of an inability to absorb vitamin B12 from food and in strict vegetarians who do not consume any foods that come from animals.

As a general rule, most individuals who develop a vitamin B12 deficiency have an underlying stomach or intestinal disorder that limits the absorption of vitamin B. Sometimes the only symptom of these intestinal disorders is subtly reduced cognitive function resulting from early vitamin B deficiency. Anemia and dementia follow later.


Signs, symptoms, and health problems associated with vitamin B12 deficiency

  • Characteristic signs, symptoms, and health problems associated with vitamin B12 deficiency include anemia, fatigue, weakness, constipation, loss of appetite, and weight loss.
  • Deficiency also can lead to neurological changes such as numbness and tingling in the hands and feet.
  • Additional symptoms of vitamin B12 deficiency are difficulty in maintaining balance, depression, confusion, dementia, poor memory, and soreness of the mouth or tongue.
  • Signs of vitamin B12 deficiency in infancy include failure to thrive, movement disorders, delayed development, and megaloblastic anemia.
Many of these symptoms are very general and can result from a variety of medical conditions other than vitamin B12 deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given.


Do pregnant and/or lactating women need extra vitamin B12?

During pregnancy, nutrients travel from mother to fetus through the placenta. Vitamin B12, like other nutrients, is transferred across the placenta during pregnancy. Breast-fed infants receive their nutrition, including vitamin B12, through breast milk. Vitamin B12 deficiency in infants is rare but can occur as a result of maternal insufficiency. For example, breast-fed infants of women who follow strict vegetarian diets have very limited reserves of vitamin B12 and can develop a vitamin B12 deficiency within months of birth. This is of particular concern because undetected and untreated vitamin B12 deficiency in infants can result in permanent neurologic damage. Consequences of such neurologic damage are severe and can be irreversible. Mothers who follow a strict vegetarian diet should consult with a pediatrician regarding appropriate use of vitamin B12 supplements for their infants and children. They should also discuss with their personal physician their own need for vitamin B12 supplements.


Who else may need a vitamin B12 supplement to prevent a deficiency?

Individuals with pernicious anemia or with gastrointestinal disorders may benefit from or require a vitamin B12 supplement. Older adults and vegetarians may benefit from a vitamin B12 supplement or an increased intake of foods fortified with vitamin B12. Some medications may decrease absorption of vitamin B12. Chronic use of those medications may result in a need for additional vitamin B12.


Individuals with pernicious anemia

Anemia is a condition that occurs when there is insufficient hemoglobin in red blood cells to carry oxygen to cells and tissues. Common signs and symptoms of anemia include fatigue and weakness. Anemia can result from a variety of medical problems, including deficiencies of vitamin B12, vitamin B6, folic acid and iron. Pernicious anemia is the name given more than a century ago to describe the then-fatal vitamin B12 deficiency anemia that results from severe gastric atrophy, a condition that prevents gastric cells from secreting intrinsic factor. Intrinsic factor is a substance normally present in the stomach. Vitamin B12 must bind with intrinsic factor before it can be absorbed and used by your body. An absence of intrinsic factor prevents normal absorption of vitamin B12 and results in pernicious anemia.

Most individuals with pernicious anemia need parenteral (deep subcutaneous) injections of vitamin B12 as initial therapy to replenish depleted body stores of vitamin B12. Vitamin B12 body stores can then be managed by a daily oral supplement of vitamin B12. A physician will manage the treatment required to maintain the vitamin B12 status of individuals with pernicious anemia.


Individuals with gastrointestinal disorders

Individuals with stomach and small intestine disorders may be unable to absorb enough vitamin B12 from food to maintain healthy body stores. Intestinal disorders that may result in malabsorption of vitamin B12 include:
  • Sprue, often referred to as celiac disease (CD), is a genetic disorder. People with CD are intolerant to a protein called gluten. In CD, gluten can trigger damage to the small intestines, where most nutrient absorption occurs. People with CD often experience nutrient malabsorption. They must follow a gluten-free diet to avoid malabsorption and other symptoms of CD.

  • Crohn's disease is an inflammatory bowel disease that affects the small intestines. People with Crohn's disease often experience diarrhea and nutrient malabsorption.

  • Surgical procedures in the gastrointestinal tract, such as surgery to remove all or part of the stomach, often result in a loss of cells that secrete hydrochloric acid and intrinsic factor. Surgical removal of the distal ileum, a section of the intestines, also can result in the inability to absorb vitamin B12. Anyone who has had either of these surgeries usually requires lifelong vitamin B12 supplements to prevent a deficiency. These individuals would be under the routine care of a physician, who would periodically evaluate vitamin B12 status and recommend appropriate treatment.

Older adults

Hydrochloric acid helps release vitamin B12 from the protein in food. This must occur before vitamin B12 binds with intrinsic factor and is absorbed in your intestines. Atrophic gastritis, which is an inflammation of the stomach, decreases the secretion of gastric juices, including hydrochloric acid. Less hydrochloric acid decreases the amount of vitamin B12 separated from proteins in foods and can result in poor absorption of vitamin B12. Decreased hydrochloric acid secretion also results in growth of normal bacteria in the small intestine. The bacteria may take up vitamin B12 for their own use, further contributing to a vitamin B12 deficiency.

Up to 30 percent of adults aged 50 years and older may have atrophic gastritis, an increased growth of intestinal bacteria, and be unable to normally absorb vitamin B12 in food. They are, however, able to absorb the synthetic vitamin B12 added to fortified foods and dietary supplements. Vitamin supplements and fortified foods may be the best sources of vitamin B12 for adults older than age 50 years.

Researchers have long been interested in the potential connection between vitamin B12 deficiency and dementia. A recent review examined correlations between cognitive skills, homocysteine levels, and blood levels of folate, vitamin B12 and vitamin B6. The authors suggested that vitamin B12 deficiency may decrease levels of substances needed for the metabolism of neurotransmitters. Neurotransmitters are chemicals that transmit nerve signals. Reduced levels of neurotransmitters may result in cognitive impairment. In 142 individuals considered at risk for dementia, researchers found that a daily supplement providing 2 milligrams (mg) folic acid and 1 mg vitamin B12, taken for 12 weeks, lowered homocysteine levels by 30%. They also demonstrated that cognitive impairment was significantly associated with elevated plasma total homocysteine. However, the decrease in homocysteine levels seen with the use of vitamin supplements did not improve cognition. It is too soon to make any recommendations, but is an intriguing area of research.


Vegetarians

The popularity of vegetarian diets has risen along with an interest in avoiding meat and meat products for environmental, philosophical, and health reasons. However, the term vegetarianism is subject to a wide range of interpretations. Some people consider themselves to be vegetarian when they avoid red meat. Others believe that vegetarianism requires avoidance of all products that come from animals, including meat, poultry, fish, eggs, and dairy foods. The most commonly described forms of vegetarianism include: "lacto-ovo vegetarians", who avoid products that come from meat, poultry, and fish but consume eggs and dairy foods; "strict vegetarians", who avoid meat, poultry, fish, eggs, and dairy foods; and "vegans", who avoid meat, poultry, fish, eggs, and dairy foods and also do not use products that come from animals such as honey, leather, fur, silk, and wool.

Strict vegetarians and vegans are at greater risk of developing vitamin B12 deficiency than lacto-ovo vegetarians and nonvegetarians because natural food sources of vitamin B12 are limited to foods that come from animals. Fortified cereals are one of the few sources of vitamin B12 from plants, and are an important dietary source of vitamin B12 for strict vegetarians and vegans. Strict vegetarians and vegans who do not consume foods that come from plants that are fortified with vitamin B12 need to consider taking a dietary supplement that contains vitamin B12 and should discuss the need for vitamin B12 supplements with their physician.

It is widely believed that vitamin B12 can be consistently obtained from nutritional yeasts. Consumers should be aware that these products may or may not contain added nutrients such as vitamin B12. Dietary supplements are regulated as foods rather than drugs, and companies that sell supplements such as nutritional yeasts fortified with vitamin B12 can legally change their formulation at any time. If you choose to supplement, select reliable sources of vitamin B12 and read product labels carefully.

When adults adopt a strict vegetarian diet, deficiency symptoms can be slow to appear. It may take years to deplete normal body stores of vitamin B12. However, breast-fed infants of women who follow strict vegetarian diets have very limited reserves of vitamin B12 and can develop a vitamin B12 deficiency within months. This is of particular concern because undetected and untreated vitamin B12 deficiency in infants can result in permanent neurologic damage. Consequences of such neurologic damage are severe and can be irreversible. There are many case reports in the literature of infants and children who suffered consequences of vitamin B12 deficiency. It is very important for mothers who follow a strict vegetarian diet to consult with a pediatrician regarding appropriate use of vitamin B12 supplements for their infants and children.

In a study involving 21 subjects with type 2 diabetes, researchers found that 17 who were prescribed Metformin experienced a decrease in vitamin B12 absorption. Researchers also found that using calcium carbonate supplements (1,200 mg/day) helped limit the effect of Metformin on vitamin B12 absorption in these individuals.

Although these medications may interact with the absorption of vitamin B12, they are necessary to take for certain conditions. It is important to consult with a physician and registered dietitian to discuss the best way to maintain vitamin B12 status when taking these medications.


Caution: Folic Acid and vitamin B12 deficiency

Folic acid can correct the anemia that is caused by vitamin B12 deficiency. Unfortunately, folic acid will not correct the nerve damage also caused by vitamin B12 deficiency. Permanent nerve damage can occur if vitamin B12 deficiency is not treated. Folic acid intake from food and supplements should not exceed 1,000 g daily in healthy individuals because large amounts of folic acid can trigger the damaging effects of vitamin B12 deficiency. Adults older than 50 years who take a folic acid supplement should ask their physician or qualified health care provider about their need for additional vitamin B12.


What is the relationship between vitamin B12 homocysteine, and cardiovascular disease?

Cardiovascular disease involves any disorder of the heart and blood vessels that make up the cardiovascular system. Coronary heart disease occurs when blood vessels which supply the heart become clogged or blocked, increasing the risk of a heart attack. Vascular damage can also occur to blood vessels supplying the brain, and can result in a stroke.

Cardiovascular disease is the most common cause of death in industrialized countries such as the United States, and is on the rise in developing countries. The National Heart, Lung, and Blood Institute of the National Institutes of Health has identified many risk factors for cardiovascular disease, including an elevated LDL-cholesterol level, high blood pressure, a low HDL-cholesterol level, obesity, and diabetes. In recent years, researchers have identified another risk factor for cardiovascular disease: an elevated homocysteine level. Homocysteine is an amino acid normally found in blood, but elevated levels have been linked with coronary heart disease and stroke. Elevated homocysteine levels may impair endothelial vasomotor function, which determines how easily blood flows through blood vessels. High levels of homocysteine also may damage coronary arteries and make it easier for blood clotting cells called platelets to clump together and form a clot, which may lead to a heart attack.

Vitamin B12, folate, and vitamin B6 are involved in homocysteine metabolism. In fact, a deficiency of vitamin B12, folate, or vitamin B6 may increase blood levels of homocysteine. Recent studies found that vitamin B12 and folic acid supplements decreased homocysteine levels in subjects with vascular disease and in young adult women. The most significant drop in homocysteine level was seen when folic acid was taken alone. A significant decrease in homocysteine levels also occurred in older men and women who took a multivitamin/ multimineral supplement for 8 weeks. The supplement taken provided 100% of Daily Values (DVs) for nutrients in the supplement.

Evidence supports a role for folic acid and vitamin B12 supplements for lowering homocysteine levels, however this does not mean that these supplements will decrease the risk of cardiovascular disease. Clinical intervention trials are underway to determine whether folic acid, vitamin B12, and vitamin B6 supplements can lower risk of coronary heart disease. It is premature to recommend vitamin B12 supplements for the prevention of heart disease until results of ongoing randomized clinical trials positively link increased vitamin B12 intake from supplements with decreased homocysteine levels and decreased risk of cardiovascular disease.


Do healthy young adults need a vitamin B12 supplement?

It is generally accepted that older adults are at greater risk of developing a vitamin B12 deficiency than younger adults. One study, however, suggests that the prevalence of vitamin B12 deficiency in young adults may be greater than previously thought. This study found that the percentage of subjects in three age groups (26-49 years, 50-64 years, and 65 years and older) with deficient blood levels of vitamin B12 was similar across all age groups but that symptoms of vitamin B12 deficiency were not as apparent in younger adults. This study also suggested that those who did not take a supplement containing vitamin B12 were twice as likely to be vitamin B12 deficient as supplement users, regardless of age group. However, people who did not use supplements but did eat fortified cereal more than 4 times per week appeared to be protected from deficient blood levels of vitamin B12. Better tools and standards to diagnose vitamin B12 deficiencies are needed to make specific recommendations about the appropriateness of vitamin B12 supplements for younger adults.


What is the health risk of too much vitamin B12?

The Institute of Medicine of the National Academies did not establish a UL for this vitamin because vitamin B12 has a very low potential for toxicity. The IOM states that "no adverse effects have been associated with excess vitamin B12 intake from food and supplements in healthy individuals". In fact, the IOM recommends that adults older than 50 years get most of their vitamin B12 from vitamin supplements or fortified food because of the high incidence of impaired absorption in this age group of vitamin B12 from foods that come from animals.


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